Chem 150 Unit 12 - Metabolism Metabolism is the sum total of all the reactions that take place in a living cell. These reactions are used to extract energy

Chem 150Chem 150Unit 12 - Unit 12 - MetabolismMetabolism

Metabolism is the sum total of all the reactions Metabolism is the sum total of all the reactions that take place in a living cell. These reactions that take place in a living cell. These reactions are used to extract energy and materials form the are used to extract energy and materials form the environment (catabolism), and to use this energy environment (catabolism), and to use this energy

and these materials to produce new molecules and these materials to produce new molecules (anabolism ) that will sustain the cell and allow (anabolism ) that will sustain the cell and allow it to to propagate itself. There are literally it to to propagate itself. There are literally thousands of reactions involved in metabolism, thousands of reactions involved in metabolism,

but we will focus our attention on a core set of but we will focus our attention on a core set of reactions that will allow us to understand some reactions that will allow us to understand some

of core principals that define metabolism. of core principals that define metabolism.

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IntroductionIntroduction

In this unit we will look at some themes which define In this unit we will look at some themes which define metabolism.metabolism.• There are literally thousands of chemical reactions that There are literally thousands of chemical reactions that

take place in a living celltake place in a living cell• If you wrote the chemical equations for all of these If you wrote the chemical equations for all of these

reactions down on a single piece of paper, it would look reactions down on a single piece of paper, it would look something like this:something like this:

View the Metabolic ChartView the Metabolic Chart

http://www.chem.uwec.edu/Chem150_S07/overheads/unit12/metabolic-chart/metabolic-chart.swf



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IntroductionIntroduction

Some of the themes include:Some of the themes include:• The reactions are arranged into The reactions are arranged into pathwayspathways, where the , where the

product for one reaction is the reactant (substrate) for the product for one reaction is the reactant (substrate) for the next reaction.next reaction.• The arrangement of reactions looks very much like a wiring diagram, The arrangement of reactions looks very much like a wiring diagram,

but instead of tracing the flow of electrons, the metabolic pathways but instead of tracing the flow of electrons, the metabolic pathways trace the flow of atoms and molecules.trace the flow of atoms and molecules.

• Every chemical reaction in metabolism is catalyzed by an Every chemical reaction in metabolism is catalyzed by an enzymeenzyme..• The enzymes are used like valves to control the flow of material The enzymes are used like valves to control the flow of material

through the pathways.through the pathways.

• Nonspontaneous reactions are driven by coupling them to Nonspontaneous reactions are driven by coupling them to spontaneous reactions.spontaneous reactions.

• An outside source of energy is needed drive metabolismAn outside source of energy is needed drive metabolism

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Pathways, Energy, and Coupled ReactionsPathways, Energy, and Coupled Reactions

Metabolic reactions are arranged in pathwaysMetabolic reactions are arranged in pathways• The product of one reaction is the substrate for the next The product of one reaction is the substrate for the next

reaction in the pathway.reaction in the pathway.• There are different topologies for metabolic pathways.There are different topologies for metabolic pathways.

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The molecules that are placed along the pathway are the The molecules that are placed along the pathway are the intermediates in the reactionsintermediates in the reactions• Other reactants and products are usually represented by Other reactants and products are usually represented by

side arrowsside arrows

• This reaction equation could also be written asThis reaction equation could also be written as

CH3 CH2

OH

ethanol

NAD+ NADH + H++ CH3 C

O

acetaldehyde

H +CH3 CH2

OH

ethanol

NAD+ NADH + H++ CH3 C

O

acetaldehyde

H +

CH3 CH2 OH

NAD+ NADH + H+

CH3 C H

O

ethanol ethanal(acetaldehyde)

alcohol aldehyde

alcohol dehydrogenaseenzyme

CH3 CH2 OH

NAD+ NADH + H+

CH3 C H

O

ethanol ethanal(acetaldehyde)

alcohol aldehyde

alcohol dehydrogenaseenzyme

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When two reactions are connected through a common When two reactions are connected through a common intermediate, they are said to be intermediate, they are said to be coupledcoupled..• The coupling of reactions allows spontaneous reactions to The coupling of reactions allows spontaneous reactions to

drive nonspontaneous reactions.drive nonspontaneous reactions.

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The phosphorylation of ADP can be coupled to the The phosphorylation of ADP can be coupled to the dephosphorylation of 1,3-Bisphosphoglycerate:dephosphorylation of 1,3-Bisphosphoglycerate:

C

C

O

O P

O

O

O

CH2

OHH

O P

O

O

O

+ H2O +

Pi

C

C

O

OH

CH2

OHH

O P

O

O

O

HO P

O

O

O

3-phosphoglycerate1,3-bisphosphoglycerate

ΔGº = -11.8 kcal/mol

C

C

O

O P

O

O

O

CH2

OHH

O P

O

O

O

+ H2O +

Pi

C

C

O

OH

CH2

OHH

O P

O

O

O

HO P

O

O

O

3-phosphoglycerate1,3-bisphosphoglycerate

ΔGº = -11.8 kcal/mol

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The phosphorylation of ADP can be coupled to the The phosphorylation of ADP can be coupled to the dephosphorylation of 1,3-Bisphosphoglycerate:dephosphorylation of 1,3-Bisphosphoglycerate:

ADP + Pi ATP + H2O ΔGº = + 7.3 kcal/mol

1,3-bisphosphoglycerate + H2O 3-phosphoglycerate + Pi ΔGº = -11.8 kcal/mol

ADP + Pi ATP + H2O ΔGº = + 7.3 kcal/mol

1,3-bisphosphoglycerate + H2O 3-phosphoglycerate + Pi ΔGº = -11.8 kcal/mol

ADP + Pi ATP + H2O1,3-bisphosphoglycerate + H2O 3-phosphoglycerate + Pi+ +ADP + Pi ATP + H2O1,3-bisphosphoglycerate + H2O 3-phosphoglycerate + Pi+ +

ADP ATP1,3-bisphosphoglycerate 3-phosphoglycerate+ +ADP ATP1,3-bisphosphoglycerate 3-phosphoglycerate+ + ΔGº = -4.5 kcal/molCH3 CH2

OH

ethanol

ΔGº = -4.5 kcal/molCH3 CH2

OH

ethanol

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Overview of MetabolismOverview of Metabolism

MetabolismMetabolism• The sum of all reactions that take place in a living The sum of all reactions that take place in a living

organism.organism.

Metabolism = Catabolism + AnabolismMetabolism = Catabolism + Anabolism

• CatabolismCatabolism - larger molecules are broken down into - larger molecules are broken down into smaller ones in a process that usually releases energysmaller ones in a process that usually releases energy

• AnabolismAnabolism - larger molecules are made from small ones in - larger molecules are made from small ones in a process the usually requires energya process the usually requires energy

View the Metabolic ChartView the Metabolic Chart




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One of the common links between catabolism and anabolism One of the common links between catabolism and anabolism is ATP.is ATP.

• ATP is used to shuttle chemical energy from catabolism to ATP is used to shuttle chemical energy from catabolism to anabolism.anabolism.

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One of the common links between catabolism and anabolism One of the common links between catabolism and anabolism is ATP.is ATP.

• ATP is used to shuttle chemical energy from catabolism to ATP is used to shuttle chemical energy from catabolism to anabolism.anabolism.

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• This is done by coupling the spontaneous reactions in This is done by coupling the spontaneous reactions in catabolism to the phosphorylation of ADP to produce ATP:catabolism to the phosphorylation of ADP to produce ATP:

• And then coupling the unfavorable reactions in anabolism And then coupling the unfavorable reactions in anabolism to the hydrolysis of ATP:to the hydrolysis of ATP:

ATP + H2OADP + Pi ∆G = +7.3 kcal/molATP + H2OADP + Pi ∆G = +7.3 kcal/mol

ATP + H2O ADP + Pi ∆G = -7.3 kcal/mol

ATP + H2O AMP + PPi ∆G = -7.6 kcal/mol

ATP + H2O ADP + Pi ∆G = -7.3 kcal/mol

ATP + H2O AMP + PPi ∆G = -7.6 kcal/mol

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The biological oxidation/reduction agents NADThe biological oxidation/reduction agents NAD++ and FAD are and FAD are also used to shuttle energy from the favorable oxidations that also used to shuttle energy from the favorable oxidations that take place in catabolism, to the unfavorable reductions that take place in catabolism, to the unfavorable reductions that take place in anabolismtake place in anabolism

A is oxidized

B is reduced

catabolismcatabolismcatabolismcatabolism anabolismanabolismanabolismanabolism

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CatabolismCatabolism• Occurs in stages.Occurs in stages.• Occupies the center of Occupies the center of

the metabolic chart.the metabolic chart.

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The reactions from Acetyl-Co and below require molecular The reactions from Acetyl-Co and below require molecular oxygen (Ooxygen (O22).).• These reactions take place in a specialized organelle These reactions take place in a specialized organelle

called the called the mitochondriamitochondria..

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DigestionDigestion

Digestion is the first stage of metaboism in which large Digestion is the first stage of metaboism in which large molecule are broken done in small molecules that can be molecule are broken done in small molecules that can be absorbed into the blood in the small intestine.absorbed into the blood in the small intestine.• Most of these reactions are hydrolysis reactionsMost of these reactions are hydrolysis reactions• Proteins are hydrolyzed in to amino acidsProteins are hydrolyzed in to amino acids• Polysaccharides are hydrolyzed into monosaccharidesPolysaccharides are hydrolyzed into monosaccharides• Triglycerides are hydrolyzed into fatty acids and glycerol.Triglycerides are hydrolyzed into fatty acids and glycerol.

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GlycolysisGlycolysis

Glycolysis is a series of 10 coupled reactionsGlycolysis is a series of 10 coupled reactions• The pathway starts with glucose that comes into a cell from The pathway starts with glucose that comes into a cell from

the blood and is immediately phosphorylated to glucose-6-the blood and is immediately phosphorylated to glucose-6-phosphate.phosphate.• The phosphorylation traps the glucose in the cell.The phosphorylation traps the glucose in the cell.

• The pathway then goes on to split (lyse) the the 6-carbon The pathway then goes on to split (lyse) the the 6-carbon glucose molecule into two 3-carbon molecules and to glucose molecule into two 3-carbon molecules and to oxidize these to oxidize these to αα-keto acids (Pyruvic acid).-keto acids (Pyruvic acid).

• The energy released in the pathway is used to produce two The energy released in the pathway is used to produce two types of energy rich molecules:types of energy rich molecules:• Two molecules of ADP are phosphorylated to ATP.Two molecules of ADP are phosphorylated to ATP.• Two molecules of NADTwo molecules of NAD++ are reduced to NADH/H are reduced to NADH/H++..

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Step 1: Glucose is brought Step 1: Glucose is brought into the cell and into the cell and phosphorylated.phosphorylated.• The phosphorylation is The phosphorylation is

coupled to the coupled to the hydrolysis of ATP.hydrolysis of ATP.

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Step 2: Glucose-6-Step 2: Glucose-6-phosphate (an phosphate (an aldohexose) is isomerized aldohexose) is isomerized to fructose-6-phosphate (a to fructose-6-phosphate (a ketohexose).ketohexose).• This reaction occurs This reaction occurs

near equilibrium, which near equilibrium, which allows it to go in either allows it to go in either direction.direction.

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Step 3: Fructose-6-Step 3: Fructose-6-phosphate is phosphate is phosphorylated to phosphorylated to fructose-1,6-bisphosphate.fructose-1,6-bisphosphate.• This reaction is coupled This reaction is coupled

to the hydrolysis of ATP.to the hydrolysis of ATP.• This sets things up for This sets things up for

the cleavage, which the cleavage, which occurs in the next step.occurs in the next step.

• So far 2 ATP’s have So far 2 ATP’s have been used instead of been used instead of produced.produced.

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Step 4: Fructose-1,6-Step 4: Fructose-1,6-bisphosphate splits into two bisphosphate splits into two three carbon three carbon monosaccharidesmonosaccharides• Glyceraldehyde-3-phophate.Glyceraldehyde-3-phophate.• Dihydroxyacetone phosphateDihydroxyacetone phosphate

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Step 5: Dihydroxyacetone phosphate is isomerized to Step 5: Dihydroxyacetone phosphate is isomerized to glyceraldehyde-3-phosphate.glyceraldehyde-3-phosphate.• The last five reactions in glycolysis start with The last five reactions in glycolysis start with

glyceraldehyde-phosphate.glyceraldehyde-phosphate.• The remaing reactions will couple the oxidation of The remaing reactions will couple the oxidation of

glyceraldhyde-3-phosphate to the production of ATP and glyceraldhyde-3-phosphate to the production of ATP and NADH/HNADH/H++..

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Step 6: Glyceraldehyde-3-Step 6: Glyceraldehyde-3-phosphate is oxidized to 1,3-phosphate is oxidized to 1,3-Bisphosphoglycerate.Bisphosphoglycerate.• The oxidation of the The oxidation of the

aldehyde to an acid is aldehyde to an acid is coupled to the reduction of coupled to the reduction of NADNAD++ to NADH/H to NADH/H++ and the and the phosphorylation of the acid phosphorylation of the acid to a mixed phosphate to a mixed phosphate anhydride.anhydride.

• The hydrolysis of a The hydrolysis of a phosphate anhydride has phosphate anhydride has a large negative a large negative ΔΔGG..

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Step 7: The hydrolysis of the Step 7: The hydrolysis of the phosphate from 1,3-phosphate from 1,3-bisphosphoglycerate is bisphosphoglycerate is coupled to the coupled to the phosphorylation of ADP to phosphorylation of ADP to generate ATPgenerate ATP• Since two 1,3-Since two 1,3-

bisphosphoglycerates are bisphosphoglycerates are produced per glucose produced per glucose molecule, the two ATP’s molecule, the two ATP’s that were invested in the that were invested in the first part of glycolysis have first part of glycolysis have now been recovered.now been recovered.

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The remaining three steps will convert the phosphate ester in The remaining three steps will convert the phosphate ester in 3-phosphoglycerate into a phosphate whose hydrolysis can 3-phosphoglycerate into a phosphate whose hydrolysis can be coupled to the phosphorylation of ADP to produce ATP.be coupled to the phosphorylation of ADP to produce ATP.• Phosphate esters do not have a large enough negative Phosphate esters do not have a large enough negative ΔΔGG

to be coupled to the phosphorylation of ADP.to be coupled to the phosphorylation of ADP.

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Step 8: 3-Phosphoglycerate Step 8: 3-Phosphoglycerate is isomerized to 2-is isomerized to 2-phosphoglycerate.phosphoglycerate.• The phosphate ester is The phosphate ester is

moved form carbon 3 to moved form carbon 3 to carbon 2.carbon 2.

• Like most isomerization Like most isomerization reactions, this reaction can reactions, this reaction can go in either direction.go in either direction.

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Step 9: 2-Phosphoglycerate Step 9: 2-Phosphoglycerate is dehydrated to form is dehydrated to form phosphoenolpyruvate.phosphoenolpyruvate.• The dehydration of the The dehydration of the

alcohol produces a double alcohol produces a double bond between carbons 2 bond between carbons 2 and 3.and 3.

• This produces a This produces a phosphate with a large phosphate with a large negative free energy for negative free energy for hydrolysis, which can now hydrolysis, which can now be coupled to the be coupled to the phosphorylation of ADP.phosphorylation of ADP.

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Step 10: The hydrolysis of the Step 10: The hydrolysis of the phosphate from phosphate from phosphoenolpyruvate is phosphoenolpyruvate is coupled to the phosphorylation coupled to the phosphorylation of ADP.of ADP.• The hydroxyl group that is The hydroxyl group that is

produced next to the carbon-produced next to the carbon-carbon double-bond carbon double-bond spontaneously isomerizes to spontaneously isomerizes to a ketone.a ketone.

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The net reaction for coupling all ten steps in glycolysis:The net reaction for coupling all ten steps in glycolysis:

• The energy released in the pathway is used to produce two The energy released in the pathway is used to produce two types of energy rich molecules:types of energy rich molecules:• Two molecules of ADP are phosphorylated to ATP.Two molecules of ADP are phosphorylated to ATP.• Two molecules of NADTwo molecules of NAD++ are reduced to NADH/H are reduced to NADH/H++..

O

OH OH

OH

OH

CH2OH

+2 NAD+ 2 ADP 2NADH/H+ 2 ATP+ + +CH3 C

O

C

O

OH2

glucose pyruvate

2 Pi+

O

OH OH

OH

OH

CH2OH

+2 NAD+ 2 ADP 2NADH/H+ 2 ATP+ + +CH3 C

O

C

O

OH2

glucose pyruvate

2 Pi+

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Fates of pyruvate when molecular oxygen cannot be used to Fates of pyruvate when molecular oxygen cannot be used to reoxidize the NADH/H+ back to NAD+.reoxidize the NADH/H+ back to NAD+.• The fermentation pathways provide away of reoxidizing The fermentation pathways provide away of reoxidizing

NADH/HNADH/H++ back to NAD back to NAD++, so that it can be used to keep , so that it can be used to keep glycolysis going.glycolysis going.

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GluconeogenesisGluconeogenesis

Gluconeogenesis is the synthesis Gluconeogenesis is the synthesis of glucose from pyruvateof glucose from pyruvate• It uses 7 out of the 10 It uses 7 out of the 10

reactions from glycolysis.reactions from glycolysis.• The remaining three have too The remaining three have too

large a negative free energy to large a negative free energy to be reversed. be reversed. • These include stepsThese include steps‣ 1, 3 and 101, 3 and 10

• Alternative reactions are used Alternative reactions are used to get around these falls.to get around these falls.

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Glycogen MetabolismGlycogen Metabolism

When glucose is not needed to meet energy needs, it can be When glucose is not needed to meet energy needs, it can be stored as the polysaccharide glycogen and used for future stored as the polysaccharide glycogen and used for future energy needs.energy needs.• The liver and the muscles are where glycogen is The liver and the muscles are where glycogen is

synthesized and stored.synthesized and stored.• The muscles store it for future muscular activity.The muscles store it for future muscular activity.• The liver stores it to help regulate blood glucose levels.The liver stores it to help regulate blood glucose levels.

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Glycogen MetabolismGlycogen Metabolism

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Citric Acid CycleCitric Acid Cycle

If an organism can utilize molecular oxygen to accept If an organism can utilize molecular oxygen to accept electrons from the reduced nucleotides NADH/Helectrons from the reduced nucleotides NADH/H++ and FADH and FADH22, , then the pyruvate from glycolysis can be completely oxidized then the pyruvate from glycolysis can be completely oxidized to COto CO22 and H and H22O.O.• These reactions occur within a cellular organelle called the These reactions occur within a cellular organelle called the

mitochondria.mitochondria.• The first step in the complete oxidation is the The first step in the complete oxidation is the

decarboxylation of pyruvate to produce Acetyl-S-CoA.decarboxylation of pyruvate to produce Acetyl-S-CoA.

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The Acetyl-CoA is fed into the citric acid cycle, where its two The Acetyl-CoA is fed into the citric acid cycle, where its two carbons are oxidized to COcarbons are oxidized to CO22..• In the processIn the process• 3 more NAD3 more NAD++ are reduced to NADH/H are reduced to NADH/H++

• 1 FAD is reduced to FADH1 FAD is reduced to FADH22

• 1 GDP is phosphorylated to GTP1 GDP is phosphorylated to GTP

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The net reaction for coupling all 8 steps in glycolysis:The net reaction for coupling all 8 steps in glycolysis:

CH3 C

O

CoA +3 NAD+ GDP+ FAD + Pi+ +3 NADH/H+ GTPFADH2 +CoA +2 CO2 +CH3 C

O

CoA +3 NAD+ GDP+ FAD + Pi+ +3 NADH/H+ GTPFADH2 +CoA +2 CO2 +

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Electron Transport Chain andElectron Transport Chain andOxidative PhosphorylatioinOxidative Phosphorylatioin

The reoxidation of the NADH/HThe reoxidation of the NADH/H++ to NAD to NAD++ and FADH and FADH22 to FAD to FAD using molecular oxygen (Ousing molecular oxygen (O22) as the oxidizing agent, is carried ) as the oxidizing agent, is carried out by the electron transport chain.out by the electron transport chain.• The electron transport chain is located within the inner The electron transport chain is located within the inner

membrane of mitochondria.membrane of mitochondria.

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The reoxidation of the NADH/HThe reoxidation of the NADH/H++ to NAD to NAD++ and FADH and FADH22 to FAD to FAD using molecular oxygen (Ousing molecular oxygen (O22) as the oxidizing agent, is carried ) as the oxidizing agent, is carried out by the electron transport chain.out by the electron transport chain.• The energy released in the reoxidation is coupled to the The energy released in the reoxidation is coupled to the

synthesis of ATP from ADP and Psynthesis of ATP from ADP and P ii by the enzyme ATP by the enzyme ATP synthase.synthase.• The coupling involves the creation of a hydrogen ion concentration The coupling involves the creation of a hydrogen ion concentration

gradient across the inner mitochondrial membrane.gradient across the inner mitochondrial membrane.• The energy for synthesizing the ATP comes from allowing the the The energy for synthesizing the ATP comes from allowing the the

hydrogen ions to flow back across the membrane.hydrogen ions to flow back across the membrane.

The EndThe End

Documents

Chem 150 Unit 12 - Metabolism Metabolism is the sum total of all the reactions that take place in a living cell. These reactions are used to extract energy